The Hopkins Lupus Cohort is a unique 27 year, 2300 SLE patient longitudinal cohort in which patients are followed by protocol every 3 months, allowing study of time-varying (lupus activity, cardiovascular risk factors and, treatment) variables: 1) In the last RO-1 we successfully developed and published computed tomography angiography (CTA) for detection of noncalcified plaque in SLE and showed that it was associated with same day measures of SLE activity. In this project, we will determine predictors of noncalcified plaque changes over time. We will bring an automated measure of noncalcified and calcified plaque burden to the clinic. 2) In the last RO-1 we successfully developed a consortium of U.S. sites interested in urine biomarkers of lupus nephritis activity, and discovered and published new biomarkers including urinary VCAM-1. In this project we have enlarged the consortium, arranged collaboration with the GlaxoSmithKline belimumab lupus nephritis clinical trial to obtain longitudinal samples, and have begun our own urinary proteomics discovery program. We have already successfully brought urinary TWEAK to clinical trial stage, and anticipate bringing a panel of urinary biomarkers to the clinic for identification of lupus nephrits activity and prediction of treatment outcome. 3) In a past collaboration with Biogen-Idec we found that BAFF and neutrophil gene signatures associate with same day SLE activity and predict activity over the next year. In this project, we will continue that collaboration and determine whether these gene signatures are invariant in an individual or whether they change over time. If they change, we will evaluate the contributions of treatments and other variables. These investigations will demonstrate the utility of these signatures in indicating and predicting disease activity over time, so that they can be used in the clinic and in clinical trials.